A novel anti-PD1 agent, tislelizumab, is under development for the treatment of patients with solid tumours and has demonstrated clinical benefit in unresectable hepatocellular carcinoma (HCC), according to findings from a phase II study presented at the ESMO World Congress on Gastrointestinal Cancer 2021, which was held from 30 June to 3 July 2021.

Ghassan K. Abou-Alfa of the Department of Medicine, Memorial Sloan Kettering Cancer Center in New York, USA explained that tislelizumab is an investigational monoclonal antibody with high affinity and binding specificity for PD1. It was specifically designed to minimise binding of the FcyR on macrophages to help abrogate antibody-dependent phagocytosis, which figures in T-cell clearance and is a potential mechanism of resistance to anti-PD1 therapy.

Supporting evidence for tislelizumab was provided in two early phase studies (NCT02407990, CTR20160872) where it was administered as monotherapy in patients with advanced solid tumours, including HCC. Both studies demonstrated preliminary anti-tumour activity with tislelizumab, which was generally well-tolerated.

The global phase II study (NCT03419897) presented at this Congress evaluated single-agent tislelizumab administered at 200 mg i.v. every 3 weeks in 249 patients with unresectable HCC. The patients’ median age was 62 years. HCC was classified as Child-Pugh A and Barcelona Clinic Liver Cancer (BCLC) stage B or C; at study entry, 225 (90%) patients had BCLC stage C and 200 (80%) had extrahepatic spread. Regarding prior systemic treatment, 111 (45%) patients had received ≥2 prior systemic therapies including sorafenib in 233 (94%) patients.

The overall response rate by independent review committee (IRC; ORRIRC) per RECIST v1.1 served as the primary endpoint and the secondary endpoints were progression-free survival by IRC (PFSIRC), ORR per investigator (ORRINV), duration of response (DoR), overall survival (OS), and the safety/tolerability profile of tislelizumab.

Response evaluations of both the independent review committee and investigator were in accord

In the overall patient population, the confirmed ORRIRC was 12.4% (95% confidence interval [CI] 8.6-17.2), which included 2 complete responses (CR) and 29 partial responses (PR). DoRIRC was not reached (NR) with median follow-up of 9.1 months.

Evaluation of the secondary endpoints provided an ORRINV of 14.1% (95% CI 10-19.0), which included 1 CR and 34 PRs.

Median OS was 12.4 months (95% CI 10.8-NR) and the one-year OS rate was 51.9% (95% CI 44-59). Median PFS was 2.7 months (95% CI 1.5-2.8).

In addition, the investigators found that the response and survival estimates were unaffected by the number of prior lines of therapy.  Patients having 1 line of previous therapy demonstrated an ORRIRC of 13.0% (95% CI 7.9-19.8) and those with ≥2 prior lines had an ORRIRC of 11.7% (95% CI 6.4-19.2). In patients with 1 prior treatment line, the median OS was 13.0 months (95% CI 10.5-NR) and median PFS was 2.6 months (95% CI 1.4, 2.8); in patients with ≥2 prior lines, the median OS and PFS were 11.8 months (95% CI 10.6-NR) and 2.7 months (95% CI 1.4-2.8), respectively.

The most common treatment-related adverse events (TRAEs) were increased AST, which occurred in 30 (12%) patients, and ALT in 2 (9%) patients. The only grade 3–4 TRAE occurring in ≥2% of patients was increased AST, which was reported in 6 (2%) patients.

Fatal AEs occurred in two patients consisting of infectious pneumonia and hepatic encephalopathy in one patient each; neither death was attributed to treatment according to the investigators.


Based on these findings, the investigators remarked that tislelizumab demonstrated durable responses and was well tolerated in patients with unresectable HCC that had been received previous systemic treatment.

They noted that these patients have a continued high unmet medical need.

They also announced that there is an ongoing large, global, randomised phase III study (NCT03412773) comparing tislelizumab with sorafenib as a reference standard in first-line treatment for adult patients with unresectable HCC.

Prof. Chris J. Verslype of the University Hospital in Leuven, Belgium, who discussed the study findings, said that it was a phase II study, however with no details on translational studies. Tislelizumab is an active and safe investigational PD1 antibody in second- and third-line setting (without prior anti-PD1/PD-L1 therapy) that is comparable to other anti-PD1 agents. In terms of further developments, Prof. Verslype commented that ongoing phase III study in first-line setting of tislelizumab versus sorafenib is unlikely to yield clinically relevant results.   

Funding from BeiGene, Ltd. was disclosed.


O–1. Ducreux M, Abou-Alfa G, Ren Z, et al. Results from a Global Phase 2 Study of Tislelizumab, an Investigational PD-1 Antibody, in Patients With Unresectable Hepatocellular Carcinoma. ESMO World Congress on Gastrointestinal Cancer 2021 (30 June – 3 July).